Urological inflammation is a significant health concern for many individuals. For example, neurogenic bladder (NGB) disease can result from excess inflammation that leads to subsequent fibrosis of the urinary bladder. In children, many congenital diseases result in NGB disease, including posterior urethral valves, bladder/cloacal exstrophy, and myelomeningocele (MMC)/Spina Bifida. NGB disease still remains one of the most common causes of renal failure and renal transplantation in children. These processes in children share overlap in adults, in whom chronic inflammatory bladder disorders such as interstitial cystitis (IC), results in significant pelvic pain and debilitating urinary symptoms. More than 4 million people in the United States have IC, with the bulk involving primarily women. The underlying physiology is based on inflammation, but the exact etiology remains elusive. Recently, the cost and disease burden associated with IC was analyzed by the Urologic Diseases in America Project and found to exceed $750 million dollars annually. Presently, the treatment of this condition has been suboptimal because of its uncertain cause and pathogenesis. A fundamental lack of understanding of the inflammatory cascades that perpetuate the disease process has resulted in a paucity of therapeutic options.
Painful bladder syndrome/interstitial cystitis (PBS/IC) is an indolent bladder disorder that has continued to be a debilitating disease with few truly effective treatment options.1-4 Affecting primarily women, PBS/IC is a chronic disease characterized by urinary frequency, bladder pain, nocturia, urgency, and pelvic pain. While the underlying physiology is based on inflammation, the disease etiology is multifactorial;4 contributing mechanisms include deficiencies in the GAG layer and mast cell-mediated neuroinflammation.5 In 1997, PBS/IC was estimated to affect approximately 1 million people in the United States;6 more recent estimates range from 0.1%4% of all women.2 Recently, the cost and disease burden associated with PBS/IC was analyzed by the Urologic Diseases in America Project and found to exceed $750 million dollars annually.7 
Two anti-inflammatory sulfated polysaccharides are currently available medical therapeutics, but neither is particularly effective. First, heparin is administered intravesically, but off-target effects, expense, and modest efficacy limit its regular usage.8-10 Second, oral Elmiron (pentosan polysulfate), alleged to replenish the GAG layer, has a long lead time for onset of efficacy, is only effective in <50% of women, is poorly bioavailable (<6% of ingested) to the bladder, and has many undesirable off-target effects.11, 12 Two other treatments include intravesical instillation of Cystistat13 (unmodified 0.04% hyaluronic acid, HA), and CystoProtek,14, 15 or 0.2% chondroitin sulfate. Options for management of PBS/IC include oral hydroxyzine, quercetin, amitriptyline, gabapentin, and narcotics; intravesical DMSO, resiniferatoxin and botox have also been used, as well as combination therapies.2-4 Reviews of therapeutic options agree that more effective treatments are needed.2, 3 
In order for the bladder to store urine it must be compliant (pliable). This means it is imperative to hold variable volumes of urine at low pressures. Failure results in elevated bladder pressure, transmitting urine to the kidney resulting in glomerular injury, renal parenchymal fibrosis and renal failure. Excess deposition of extracellular matrix (ECM) within the bladder wall is the main mechanism for loss of bladder wall pliability. This fibrosis can result from multiple mechanisms, one of which includes chronic inflammation. In response, bladder fibrosis is part of a wound healing process with accumulation of ECM proteins (collagen types I and III). Also, during chronic tissue inflammation, damage to fibroblasts and myofibroblasts activates cell proliferation, motility, contractility, and ECM synthesis. The final result is fibrosis, loss of compliance, and bladder dysfunction
Other conventionally accepted treatments of inflammation may involve UV phototherapy, corticosteroids and glucocorticoids, acitretin, cyclosporine, and methotrexate. However, each of these treatments may cause serious side effects ranging from immune suppression and liver disease to thinning skin and causing birth defects. Due to partial or complete ineffectiveness, these treatments often leave patients unsatisfied with their results.
As indicated above, heparin treatment has also been experimentally explored. Heparin, a sulfated polysaccharide, has traditionally been used almost exclusively as an anti-coagulant, but its anti-inflammatory properties are well known. Heparin and its derivatives have shown some promise in treating these inflammatory diseases. Particularly heparin and its derivatives disrupt at least three important events in inflammatory cascades. First, heparin attaches to and blocks the leukocyte integrins P- and L-selectin. Second, heparin and its derivatives reduce the inflammatory cascade by binding to and inhibiting the cationic PMN protease human leukocyte elastase and cathepsin G, which reduces proteolytic tissue injury by PMNs that escape the first heparin barrier of selectin inhibition. Third, heparin and its derivatives potentially inhibit the interaction of the receptor for advanced glycation end-products (RAGE) with its ligands.
Although heparin and its derivatives have shown promise in treating inflammation, treatment with heparin and its derivatives exhibits several major drawbacks. First, heparin and its derivatives are porcine-derived; thus leading to concerns of cross-species transfer of viruses. Second, because of heparin's anticoagulant properties, diabetics treated with this compound are at risk of excessive bleeding. Third, heparin may induce thrombocytopenia in certain individuals who produce an antibody to the complex of heparin with the cationic protein platelet factor-4 (PF-4), resulting in catastrophic platelet aggregation and generalized paradoxical arterial and venous clotting. Thus, an important unmet need is to formulate compounds which may be used to treat urological inflammation while avoiding the myriad of side effects seen in other treatments.